tbuckley/cabot-search huggingface dataset:
Abundant Aβ fibrils in ultracentrifugal supernatants of aqueous extracts from Alzheimer’s disease brains
Authors: Andrew M. Stern, Yang Yang, Shanxue Jin, Keitaro Yamashita, Angela L. Meunier, Wen Liu, Yuqi Cai, Maria Ericsson, Lei Liu, Michel Goedert, Sjors H.W. Scheres, Dennis J. Selkoe
Journal: Neuron (2023)

Soluble oligomers of amyloid β-protein (Aβ) have been defined as aggregates in supernatants following ultracentrifugation of aqueous extracts from Alzheimer's disease (AD) brains and are believed to be upstream initiators of synaptic dysfunction, but little is known about their structures. We now report the unexpected presence of Aβ fibrils in synaptotoxic high-speed supernatants from AD brains extracted by soaking in an aqueous buffer. The fibrils did not appear to form during preparation, and their counts by EM correlated with Aβ ELISA quantification. Cryo-EM structures of aqueous Aβ fibrils were identical to those from sarkosyl-insoluble homogenates. The fibrils in aqueous extracts were labeled by lecanemab, an Aβ aggregate-directed antibody reported to improve AD cognitive outcomes. Lecanemab provided protection against aqueous fibril synaptotoxicity. We conclude that fibrils are abundant in aqueous extracts from AD brains and have the same structures as those from plaques. These findings have implications for AD pathogenesis and drug design.
An integrated therapeutic approach to sickle cell disease management beyond infancy
Authors: Jean‐Antoine Ribeil, Galia Pollock, Haydar Frangoul, Martin H. Steinberg
Journal: American Journal of Hematology (2023)

Hydroxyurea, the first approved drug for sickle cell disease, decreases sickle hemoglobin polymerization by inducing fetal hemoglobin. Its effects in young children are excellent; responses in adults are variable and not curative. The goal of pharmacotherapy should not be disease "moderation" but reducing morbidity and mortality by diminishing both hemolytic anemia and vaso-occlusive events. This is best done by preventing sickle hemoglobin polymerization; if anti-polymerization treatment is insufficient, agents disrupting pathophysiologic pathways "downstream" of the sickle hemoglobin polymer should be added. We recommend that all patients should be started first on maximal doses of hydroxyurea. When the clinical and hematologic response to hydroxyurea is insufficient, as it is almost always in adults, we favor adding voxelotor, a hemoglobin-oxygen affinity-shifting agent that, likely in a pancellular distribution, decreases sickle hemoglobin polymerization. The P-selectin inhibitor crizanlizumab reduces sickle cell-endothelial interactions and can be used in patients with continued vaso-occlusive events. There is no physiologic reason that all three drugs could not be combined when the response to monotherapy or dual-drug therapy is poor. Drug therapy must be considered in the context of possibly "curative" cellular therapeutics and if needed, exchange transfusion programs.
Efficacy and safety of dupilumab in patients with severe chronic hand eczema with inadequate response or intolerance to alitretinoin: a randomized, double-blind, placebo-controlled phase IIb proof-of-concept study
Authors: Angelique N Voorberg, Esmé Kamphuis, Wietske A Christoffers, Marie L A Schuttelaar
Journal: British Journal of Dermatology (2023)

Effective treatment options for patients with chronic hand eczema (CHE) are scarce. Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis and has shown promising results for the treatment of hand eczema in other studies.
Effect of Immediate Referral vs a Brief Problem-solving Intervention for Screen-Detected Peripartum Depression
Authors: Mei Elansary, Caroline J. Kistin, Jocelyn Antonio, Ivys Fernández-Pastrana, Aviva Lee-Parritz, Howard Cabral, Emily S. Miller, Michael Silverstein
Journal: JAMA Network Open (2023)

Importance The US Preventive Services Task Force recommends screening adults for depression in settings with programs in place to ensure receipt of appropriate care. Best practices regarding how to ensure such care are unknown, particularly for pregnant and postpartum persons. Objective To compare the effectiveness of 2 strategies for the initial management of screen-detected peripartum depressive symptoms. Design, Setting, and Participants This randomized comparative effectiveness trial was performed from February 1, 2018, to June 30, 2020, at the prenatal clinic, postpartum unit, and pediatric clinic within an urban safety-net hospital. Participants included peripartum persons with positive depression screen results. Data were analyzed from July 6, 2020, to September 21, 2022, based on intention to treat. Interventions Engagement-focused care coordination (EFCC), which used shared decision-making and motivational techniques to refer patients to outside mental health services, and problem-solving education (PSE), a brief cognitive-behavioral program delivered at the screening site. Main Outcomes and Measures The primary outcome consisted of severity of depressive symptoms; secondary outcomes included severity of anxiety symptoms and engagement with care, each measured bimonthly over 12 months. Rates of symptom elevations were modeled using negative binomial regression; rates of symptom trajectories were modeled using treatment × time interactions. Results Among the 230 participants (mean [SD] age, 29.8 [5.8] years), 125 (54.3%) were Black and 101 (43.9%) were Hispanic or Latina. At baseline, 117 participants (50.9%) reported at least moderately severe depressive symptoms (Quick Inventory of Depressive Symptomatology score ≥11), and 56 (24.3%) reported clinically significant anxiety symptoms (Beck Anxiety Inventory score ≥21). Across 6 assessment time points, the mean (SD) number of moderately severe depressive symptom episodes in EFCC was 2.2 (2.2), compared with 2.2 (2.1) in PSE, for an adjusted rate ratio (aRR) of 0.95 (95% CI, 0.77-1.17). The mean (SD) number of anxiety symptom elevations in EFCC was 1.1 (1.8), compared to 1.1 (1.6) in PSE, for an aRR of 0.98 (95% CI, 0.69-1.39). There were significant treatment × time interactions relative to mean depressive symptom scores (−0.34 [95% CI, −0.60 to −0.08]; P = .009 for interaction term), favoring EFCC. There were no differences in engagement with care. Conclusions and Relevance In this randomized comparative effectiveness trial, there were no differences in depressive or anxiety symptom burden across comparators; however, the evidence suggested improved depressive symptom trajectory with immediate referral. Further work is necessary to guide approaches to management following depression screening for peripartum persons. Trial Registration ClinicalTrials.gov Identifier: NCT03221556
Is It Just for a Screening Program to Give People All the Information They Want?
Authors: Lisa Dive, Isabella Holmes, Ainsley J. Newson
Journal: The American Journal of Bioethics (2023)

Genomic screening at population scale generates many ethical considerations. One is the normative role that people's preferences should play in determining access to genomic information in screening contexts, particularly information that falls beyond the scope of screening. We expect both that people will express a preference to receive such results and that there will be interest from the professional community in providing them. In this paper, we consider this issue in relation to the just and equitable design of population screening programs like reproductive genetic carrier screening (RGCS). Drawing on a pluralistic public health ethics perspective, we claim that generating and reporting information about genetic variants beyond the scope of the screening program usually lacks clinical, and perhaps personal, utility. There are both pragmatic and ethical reasons to restrict information provision to that which fits the stated purpose of the program.
Multistate Outbreak of <i>Salmonella</i> Thompson Infections Linked to Seafood Exposure — United States, 2021
Authors: Ann Q. Shen, Alyssa Dalen, Laura Bankers, Shannon R. Matzinger, Colin Schwensohn, Kane Patel, Kelley B. Hise, Evelyn Pereira, Jennifer Cripe, Rachel H. Jervis
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

In July 2021, the Colorado Department of Public Health and Environment (CDPHE) laboratory identified a cluster of five Salmonella enterica serotype Thompson isolates related to one another within one allele difference, using whole genome multilocus sequence typing (wgMLST). These five isolates, submitted to the public health laboratory as is routine process for confirmatory testing of Salmonella, were highly related to those identified in a 2020 multistate investigation, during which traceback was conducted for sushi-grade tuna and salmon; a common supplier was not identified. The 2021 investigation commenced on August 5, 2021, with five patients living in Colorado, and one each in Missouri, Washington, and Wisconsin. During August-December 2021, CDC, CDPHE, public health and regulatory officials in several states, and the Food and Drug Administration (FDA) conducted epidemiologic, environmental, and laboratory investigations of this multistate outbreak of Salmonella Thompson. Isolates were genetically related to one another and to 2020 isolates within zero to one allele difference. Implicated seafood products were traced to a single seafood distributor, in which the outbreak strain was identified through environmental sampling, and in which inspection identified inadequate sanitization and opportunities for cross-contamination of raw fish. The distributor issued a voluntary recall of 16 seafood items with high potential for contamination and completed remediation actions. This outbreak illustrated the importance of effective cleaning and sanitizing procedures and implementation of controls. When multiple products are recalled during an outbreak investigation, collaboration between public health agencies and implicated facilities can help provide food safety information to restaurants, retailers, and consumers, and to ensure disposal of all recalled products.
Measuring stillbirth and perinatal mortality rates through household surveys: a population-based analysis using an integrated approach to data quality assessment and adjustment with 157 surveys from 53 countries
Authors: Mohamed M Ali, Saverio Bellizzi, Ties Boerma
Journal: The Lancet Global Health (2023)

BackgroundIn most low-income and middle-income countries (LMICs), national surveys are the main data source for stillbirths and perinatal mortality. Data quality issues such as under-reporting and misreporting have greatly limited the usefulness of such data. We aimed to enhance the use of mortality data in surveys by proposing data quality metrics and exploring adjustment procedures to obtain the best possible measure of perinatal mortality.MethodsWe performed a population-based analysis of data from 157 demographic and health surveys (DHSs) from 1990 to 2020, with reproductive calendar and birth history data from 53 LMICs. Pregnancies terminated before 7 months' gestation were excluded. We examined data quality and compared survey values with reference values obtained from a literature review to assess misreporting of the age at early neonatal death, omission and transference of stillbirths, and very early neonatal deaths. Real cohort life-table rates of stillbirth, early neonatal, and perinatal mortality per 1000 births were calculated. The underlying risks of stillbirth and daily deaths were modelled using modified Gompertz-Makeham models.FindingsData for 2 008 807 pregnancies of ≥7 months' gestational age were extracted from the reproductive calendar for the analysis period. Age heaping at day 7 occurred in most surveys. The median value for the heaping index of deaths at day 7 was 2·05 (IQR 1·36–2·87). The median ratio of stillbirths to deaths on days 0–1 was 1·15 (0·86–1·51). Of the 157 surveys, 23 (15%) were considered to have plausible ratios, 71 (45%) had probable ratios, and 63 (40%) had improbable ratios. The ratio of deaths on days 0–1 to deaths on days 2–6 varied considerably between surveys and 119 surveys (76%) had ratios of less than 2·4, indicative of under-reporting of very early neonatal deaths in most surveys. The fully adjusted model increased the median stillbirth rates from 12·2 (9·4–15·9) to 25·6 (18·0–33·4) per 1000 births, with a median relative increase of 95·0% (56·6–136·6). The median perinatal mortality rate also increased from 32·6 (23·6–38·3) to 44·8 (32·8–58·0) per 1000 births, with a median relative increase of 47·8% (6·9–61·0).InterpretationA simultaneous focus on stillbirths and early neonatal mortality facilitates a comprehensive assessment of inaccurate reporting in household surveys and allows for better use of surveys in planning and monitoring of efforts to reduce stillbirths and early neonatal mortality.FundingNone.
4D Printing of Personalized‐Tunable Biomimetic Periosteum with Anisotropic Microstructure for Accelerated Vascularization and Bone Healing
Authors: Chao Liu, Yiting Lou, Zheyuan Sun, Haiying Ma, Mouyuan Sun, Shengjie Li, Dongqi You, Junjie Wu, Binbin Ying, Wanghui Ding, Mengfei Yu, Huiming Wang
Journal: Advanced Healthcare Materials (2023)

An ideal biomimetic periosteum is expected to wrap various bone surfaces to orchestrate an optimal microenvironment for bone regeneration, including facilitating local vascularization, recruiting osteoblasts, and mineralizing the extracellular matrix (ECM). To mimic the role of the natural periosteum in promoting bone repair, a 4D printing technique to inlay aligned cell sheets on shape-shifting hydrogel is used, containing biophysical signals and spatially adjustable physical properties, for the first time. The outer hydrogel layer endows the biomimetic periosteum with the ability to digitally coordinate its 3D geometry to match the specific macroscopic bone shape to maintain a bone healing microenvironment. The inner aligned human mesenchymal stem cells (hMSCs) layer not only promotes the migration and angiogenesis of co-cultured cells but also exhibits excellent osteogenic differentiation properties. In vivo experiments show that apart from morphing preset shapes as physical barriers, the aligned biomimetic periosteum can actively facilitate local angiogenesis and early-stage osteogenesis. Altogether, this present work provides a novel route to construct a personalized biomimetic periosteum with anisotropic microstructure by introducing a tunable shape to maintain the bone reconstruction microenvironment and this strategy can be extended to repair sophisticated bone defects.
Mental Health Care Use Among Children and Adolescents With High Health Care Costs in Ontario, Canada
Authors: Claire de Oliveira, Tomisin Iwajomo, Paul Kurdyak
Journal: JAMA Network Open (2023)

Importance Research on patients with high health care costs has examined mainly adults, with little focus on mental health care use. Objective To examine the characteristics and costs of children and adolescents with high health care costs who use mostly mental health care and whether and why they persist in the high-cost state. Design, Setting, and Participants This population-based, retrospective cohort study used health care records from Ontario, Canada, on all children and adolescents (age 0-17 years) covered under a universal health care system from January 1, 2012, to December 31, 2019. All children and adolescents in and above the 90th percentile of the cost distribution in 2012 for whom costs related to mental health care accounted for 50% or more of their costs were defined as patients with high mental health care costs. Data were analyzed from August 2019 to December 2022. Exposures High health care costs. Main Outcomes and Measures Patients with high mental health care costs were characterized in terms of their sociodemographic characteristics; chronic physical health, mental health, and behavioral conditions; and health care costs (in 2021 Canadian dollars) by health service and type of care (mental health care vs non–mental health care). Patients were followed up until 2019 to assess whether they persisted in the high-cost state and to examine factors associated with persisting in that state. Results In 2012, there were 273 490 children and adolescents with high health care costs (mean [SD] age, 6.43 [5.99] years; 55.8% male; mean cost, $7936.40; 95% CI, $7850.30-$8022.40). Of these, 20 463 (7.5%) were classified as having high mental health care costs (mean cost, $10 040.20; 95% CI, $9822.80-$10 257.50). Asthma (30.3%), attention-deficit/hyperactivity disorder (35.8%), and mood and/or anxiety disorders (94.9%) were the most common chronic physical, behavioral, or mental health conditions. Few patients with high mental health care costs persisted in the high-cost state beyond 3 years (19.0%). Mood and/or anxiety disorders (relative risk ratio [RRR], 6.17; 95% CI, 3.19-11.96) and schizophrenia spectrum disorders (RRR, 2.98; 95% CI, 2.14-4.14) were identified as the main factors associated with persistence in the high-cost state. Conclusions and Relevance In this cohort study of children and adolescents with high health care costs, some patients had high levels of mental health care use and high costs of care, but few of these persisted in the high-cost state for 3 or more years. These findings may help inform the development of care coordination interventions and service delivery models, such as youth integrated services, to reduce costs and improve outcomes for children and adolescents.
Perspectives on the Intersection of Electronic Health Records and Health Care Team Communication, Function, and Well-being
Authors: Alexis Amano, Cati G. Brown-Johnson, Marcy Winget, Amrita Sinha, Shreya Shah, Christine A. Sinsky, Christopher Sharp, Tait Shanafelt, Kelley Skeff
Journal: JAMA Network Open (2023)

Importance Understanding of the interplay between the electronic health record (EHR), health care team relations, and physician well-being is currently lacking. Approaches to cultivate interpersonal interactions may be necessary to complement advancements in health information technology with high-quality team function. Objective To examine ways in which the EHR, health care team functioning, and physician well-being intersect and interact. Design, Setting, and Participants Secondary qualitative analysis of semistructured interview data from 2 studies used keyword-in-context approaches to identify excerpts related to teams. Thematic analysis was conducted using pattern coding, then organized using the relationship-centered organization model. Two health care organizations in California from March 16 to October 13, 2017, and February 28 to April 21, 2022, participated, with respondents including attending and resident physicians. Main Outcome and Measures Across data sets, themes centered around the interactions between the EHR, health care team functioning, and physician well-being. The first study data focused on EHR-related distressing events and their role in attending physician and resident physician emotions and actions. The second study focused on EHR use and daily EHR irritants. Results The 73 respondents included attending physicians (53 [73%]) and resident physicians (20 [27%]). Demographic data were not collected. Participants worked in ambulatory specialties (33 [45%]), hospital medicine (10 [14%]), and surgery (10 [14%]). The EHR was reported to be the dominant communication modality among all teams. Interviewees indicated that the EHR facilitates task-related communication and is well suited to completing simple, uncomplicated tasks. However, EHR-based communication limited the rich communication and social connection required for building relationships and navigating conflict. The EHR was found to negatively impact team function by promoting disagreement and introducing areas of conflict into team relationships related to medical-legal pressures, role confusion, and undefined norms around EHR-related communication. In addition, interviewees expressed that physician EHR-related distress affects interactions within the team, eroding team well-being. Conclusions and Relevance In this study, the EHR supported task-oriented and efficient communication among team members to get work done and care for patients; however, participants felt that the technology shifts attention away from the human needs of the care team that are necessary for developing relationships, building trust, and resolving conflicts. Interventions to cultivate interpersonal interactions and team function are necessary to complement the efficiency benefits of health information technology.
Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India
Authors: Nilakshi Vaidya, Bharath Holla, Jon Heron, Eesha Sharma, Yuning Zhang, Gwen Fernandes, Udita Iyengar, Alex Spiers, Anupa Yadav, Surajit Das, Sanjit Roy, Chirag K. Ahuja, Gareth J. Barker, Debasish Basu, Rose Dawn Bharath, Matthew Hickman, Sanjeev Jain, Kartik Kalyanram, Kamakshi Kartik, Murali Krishna, Ghattu Krishnaveni, Kalyanaraman Kumaran, Rebecca Kuriyan, Pratima Murthy, Dimitri Papadopoulos Orfanos, Meera Purushottam, Sunita Simon Kurpad, Lenin Singh, Roshan Singh, B. N. Subodh, Mireille Toledano, Henrik Walter, Sylvane Desrivières, Amit Chakrabarti, Vivek Benegal, Gunter Schumann, Mathew Varghese, Kandavel Thennarasu, Urvakhsh Metha, Satish Girimaji, Preeti Jacob, Deepak Jayarajan, Keshav Kumar, Gitanjali Narayanan, Madhu Khullar, Niranjan Khandelwal, Abhishek Ghosh, Nainesh Joshi, Ningthoujam Debala Chanu, Fujica M.C., Victoria Ph., Celina Phurailatpam, Debangana Bhattacharya, Bidisha Haque, Alisha Nagraj, Arpita Ghosh, Anirban Basu, Mriganka Pandit, Subhadip Das, Pawan Maurya, Amritha Gourisankar, Geetha Rani T, Sujatha B, Madhavi Rangaswamy, Caroline Fall, Kiran KN, Ramya MC, Chaitra Urs, Santhosh N, Somashekhara R, Divyashree K, Arathi Rao, Poornima R, Saswathika Tripathy, Neha Parashar, Nayana K B, Ashwini Seshadri, Sathish Kumar, Suneela Baligar, Thamodaran Arumugam, Apoorva Safai, Anthony Cyril, Ashika Roy, Dhanalakshmi D, Shivamma D, Bhavana B R
Journal: JAMA Network Open (2023)

Arsenic, a contaminant of groundwater and irrigated crops, is a global public health hazard. Exposure to low levels of arsenic through food extends well beyond the areas with high arsenic content in water.